US20030032171A1 - Automated random access microbiological analyzer - Google Patents
Automated random access microbiological analyzer Download PDFInfo
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- US20030032171A1 US20030032171A1 US09/924,221 US92422101A US2003032171A1 US 20030032171 A1 US20030032171 A1 US 20030032171A1 US 92422101 A US92422101 A US 92422101A US 2003032171 A1 US2003032171 A1 US 2003032171A1
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- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
- G01N35/00584—Control arrangements for automatic analysers
- G01N35/0092—Scheduling
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
- G01N35/02—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor using a plurality of sample containers moved by a conveyor system past one or more treatment or analysis stations
- G01N35/025—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor using a plurality of sample containers moved by a conveyor system past one or more treatment or analysis stations having a carousel or turntable for reaction cells or cuvettes
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
- G01N35/00029—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor provided with flat sample substrates, e.g. slides
- G01N2035/00039—Transport arrangements specific to flat sample substrates, e.g. pusher blade
- G01N2035/00049—Transport arrangements specific to flat sample substrates, e.g. pusher blade for loading/unloading a carousel
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
- G01N35/00029—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor provided with flat sample substrates, e.g. slides
- G01N2035/00099—Characterised by type of test elements
- G01N2035/00148—Test cards, e.g. Biomerieux or McDonnel multiwell test cards
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- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
- G01N2035/00465—Separating and mixing arrangements
- G01N2035/00524—Mixing by agitating sample carrier
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
- G01N35/00584—Control arrangements for automatic analysers
- G01N35/00722—Communications; Identification
- G01N35/00732—Identification of carriers, materials or components in automatic analysers
- G01N2035/00742—Type of codes
- G01N2035/00752—Type of codes bar codes
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- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
- G01N35/00584—Control arrangements for automatic analysers
- G01N35/0092—Scheduling
- G01N2035/0093—Scheduling random access not determined by physical position
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
- G01N35/02—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor using a plurality of sample containers moved by a conveyor system past one or more treatment or analysis stations
- G01N35/04—Details of the conveyor system
- G01N2035/0439—Rotary sample carriers, i.e. carousels
- G01N2035/0446—Combinations of the above
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- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
- G01N35/02—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor using a plurality of sample containers moved by a conveyor system past one or more treatment or analysis stations
- G01N35/04—Details of the conveyor system
- G01N2035/046—General conveyor features
- G01N2035/0465—Loading or unloading the conveyor
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
- G01N35/02—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor using a plurality of sample containers moved by a conveyor system past one or more treatment or analysis stations
- G01N35/026—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor using a plurality of sample containers moved by a conveyor system past one or more treatment or analysis stations having blocks or racks of reaction cells or cuvettes
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Abstract
Description
- The present invention relates to an automated microbiological analyzer for determining both the identity of an infecting microorganism and the concentration of an antibiotic effective in controlling growth of the microorganism. More particularly, the present invention provides a microbiological analyzer with the ability to automatically and randomly supply appropriate analytical devices for different types of microorganism identity determinations as well as appropriate reagents and test arrays for different types of microorganism antibiotic determinations.
- Various types of tests related to patient diagnosis and therapy can be performed by analysis of a biological sample. Biological samples containing the patient's microorganisms are taken from a patient's infections, bodily fluids or abscesses and are typically placed in test panels or arrays, combined with various reagents, incubated, and analyzed to aid in treatment of the patient. Automated biochemical analyzers have been developed to meet the needs of health care facilities and other institutions to facilitate analysis of patient samples and to improve the accuracy and reliability of assay results when compared to analysis using manual operations. However, with ever changing bacterial genera and newly discovered antibiotics, the demand for biochemical testing has increased in both complexity and in volume. Additionally, commercial analyzers typically require a user to employ a test panel having predetermined assay types thereon regardless of whether or not all of the predetermined assay types have been requested by a physician. Because of these greater demands in conjunction with the expense and scarcity of floor space within health care institutions and the pressure to provide clinical results at lower costs, it has become important to randomly perform different types of biochemical tests within a highly automated and compact analyzer that operates at high through-put with minimal clinician attention.
- An important family of automated microbiological analyzers function as a diagnostic tool for determining both the identity of an infecting microorganism and of an antibiotic effective in controlling growth of the microorganism. In performing these tests, identification and in vitro antimicrobic susceptibility patterns of microorganisms isolated from biological samples are ascertained. Such analyzers have historically placed a small sample to be tested into a plurality of small sample test wells in panels or arrays that typically contain different enzyme substrates or antimicrobics in serial dilutions. Identification (ID) of microorganisms and of Minimum Inhibitory Concentrations (MIC) of an antibiotic effective against the microorganism are determined by color changes, fluorescence changes, or the degree of cloudiness (turbidity) in the sample test wells created in the arrays. By examining the signal patterns generated, both AST and ID measurements and subsequent analysis are performed by computer controlled microbiological analyzers to provide advantages in reproducibility, reduction in processing time, avoidance of transcription errors and standardization for all tests run in the laboratory.
- In ID testing of a microorganism, a standardized dilution of the patient's microorganism sample, known as an inoculum, is first prepared in order to provide a bacterial or cellular suspension having a predetermined known concentration. This inoculum is placed in an analytical test array or panel having a number of microwells or alternately into a cuvette rotor assembly having an inoculum receiving well from where sample is distributed by centrifugal force to a number of test wells or chambers at the periphery of the rotor. The test wells contain predetermined identification media consisting of enzyme substrates and/or growth inhibitors, which, depending on the species of microorganism present, will exhibit color changes, increases in turbidity or changes in fluorescence after incubation. For instance, a bacterial genera may be identified on the basis of pH changes, its ability to utilize different carbon compounds, or growth in the presence of antimicrobial agents in a test well. Some tests require addition of reagents to detect products of bacterial metabolism while others are self-indicating. In conventional chromogenic panels, the inoculum is incubated some 18-24 hours before analysis is completed. Alternately, microorganism ID may be accomplished using rapid fluorogenic test arrays employing growth-independent means in which preformed enzyme substrates are placed in the test wells and fluorogenic tests based on the detection of hydrolysis of fluorogenic substrates, pH changes following substrate utilization, production of specific metabolic substrates and the rate of production of specific metabolic byproducts are made after about 2 hours of incubation. In both cases, by examining the reaction of the inoculum and reagents after incubation and over a period of time, or lack thereof, and comparing that reaction with that of known species, the types of microorganisms can be identified. Importantly, a large number of different substrates or other reagents must be available in ID testing of an unknown microorganism because the microorganism will be more or less different sensitive to different substrates and reagents. In an automated analyzer, this is achieved by providing a variety of ID test panels, each pre-loaded with substrates and reagents that are selected to produce a known pattern of measurable reaction signals for various microorganisms.
- The use of microbiological test trays and the techniques employed in MIC tests, also known as antibiotic susceptibility testing, AST, of microorganisms are also well known. AST tests are essentially broth dilution susceptibility tests using wells filled with inoculum and a growth broth, called herein a inoculum-broth solution, and increasing concentrations of a number of different antibiotics, or antimicrobial agents as used in different AST tests to determine which antimicrobial agents are most effective against a particular microorganism. The different antimicrobial agents are typically diluted in Mueller-Hinton broth with calcium and magnesium in chromogenic panels or diluted in autoclaved water with a fluorogenic compound in fluorogenic panels. The antimicrobials are diluted to concentrations that include those of clinical interest. After incubation, the turbidity or fluorescence will be less or non-existent in wells where growth has been inhibited by the antimicrobics in those wells. The analyzer compares each test well reading with a threshold value. The threshold value is a fixed number corresponding to a certain percentage of relative absorbency or fluorescence which corresponds to clinically significant growth. The MIC of each antimicrobial agent is measured either directly as visible growth, or indirectly as an increase in fluorescence.
- Important challenges that must be taken into consideration when designing cost-effective, automated biochemical analyzers include the volume of reagents required per test and the cost of the disposable test panel, array or, in certain designs, a centrifugal test rotor. Because they are small and may be produced using mass-production, plastic injection molding techniques, it is advantageous to use very small sized, test arrays having a number of microwells for performing AST tests in order to facilitate automatic handling and minimize the expense of a disposable test array. AST test arrays typically consist of a plurality of adjacent microwells aligned in some sort of an array that function as reaction vessels for the above mentioned biochemical reactions involving a solid phase media and a liquid phase containing a sample to be tested. An aliquot of the sample is placed in each microwell along with appropriate antibiotic reagents. AST testing usually requires that the test trays be incubated at a controlled temperature for a period of time so that an observable reaction between the sample and reagent occurs; at predetermined time intervals, each microwell of the test tray is examined for an indication of changes in color change, turbidity, or size.
- Filling a number of AST microwells with the required inoculum and/or reagents to perform AST tests with a wide variety of antibiotics presents several technical challenges that are made increasingly difficult as the number of the available antibiotics is increased. Efforts have been made to address these challenges along with other problems and these generally employ a vacuum technique in filling microwells within a test array via an interconnected number of micro-sized channels connected between the microwells and an inoculum reservoir.
- Similarly, providing a number of ID test devices with the required substrates and/or reagents to perform ID tests to identify a wide variety of microorganisms presents technical challenges that are made increasingly difficult as the number of the available ID substrates and/or reagents is increased. Centrifugal ID test rotors like those used in the present invention typically consist of a plurality of test microwells that function as reaction vessels or microwells arrayed near the periphery of a generally flat disk. A centrifugally activated microwell filling process is employed as the ID test rotor has a large number of micro-sized channels radially connecting the test microwells to a supply reservoir near the center of the rotor. Test samples are placed within the supply reservoir and moved by centrifugal force through the microchannels to the test microwells which have been pre-loaded with appropriate biochemical reagents. The ID test rotor is generally incubated at a controlled temperature for a period of time to cause an observable reaction between the sample and reagents. At predetermined time intervals, each microwell of the ID rotor is examined for an indication of changes in color change, turbidity, or other observable reaction result. The pattern of changes may then be compared with reaction signal patterns of known microorganisms enabling the identification of the any microorganism within the sample, as discussed above.
- There are conventional devices that carry out multi-step analytical procedures in an automated or semi-automated fashion. For example, microbiological analytical systems currently carry out automated antimicrobic susceptibility testing procedures using both photometric and fluorometric detection methods. The MicroScan Division of Dade Behring Inc. sells a device of this type under the trade designation WalkAway® analyzer. Armes et al. U.S. Pat. No. 4,676,951 and Hanaway U.S. Pat. Nos. 4,643,879 and 4,681,741 describe certain features the WalkAway® analyzer. Prior commercial embodiments of the Walk-Away system analyze trays carrying microbiologic specimens. The system includes an enclosed incubation chamber for the specimens. The system adds reagents to the specimens and analyzes them. All these activities take place within the incubation chamber. Automated features of more recent microbiological testing machines are well known in the art, having been described in the following patents from which it may be seen that functions such as automated handling and transport of test devices like panels and rotors throughout an analyzer are well known. Those skilled in the art have a variety of well-known techniques and choices for the routine tasks of reagent and sample handling, test device transport, vacuum loading, incubation, optical testing, computer control, etc., as described in the patent below.
- U.S. Pat. No. 6,096,272 discloses a diagnostic microbiological testing system and method for microorganism identification (ID) and antimicrobial susceptibility determinations (AST). The system includes multiple-well test panels capable of performing ID and AST testing on the same test panel. Each test panel is inoculated with reagents, broth-suspended organisms, and placed into the instrument system. The instrument system includes a rotating carousel for incubation and indexing, multiple light sources each emitting different wavelength light, colorimetric and fluorometric detection, barcode test panel tracking and a control processor for making determinations based on measured test data.
- U.S. Pat. No. 6,086,824 discloses an automatic sample testing machine for testing samples stored in test cards. The test sample cards are placed in a tray and a transport station transports the tray from the incubation station to an optical reading station, where the cards are removed from the tray and optical measurements (e.g., transmittance and/or fluorescence optical testing) are conducted on test wells within the card. The machine has a sample loading station where test samples are placed in fluid communication with test cards in the trays.
- U.S. Pat. No. 5,965,090 provides an automatic sample testing machine for testing samples stored in test cards. The machine has a test sample positioning system for moving a tray containing a plurality of test sample cards and fluid receptacles among various stations in the machine. The machine has a diluting station for adding a predetermined quantity of diluent to the receptacles. A pipetting station transfers fluid from one receptacle to another. A vacuum filling station has a vacuum chamber which cooperates with the tray to make a seal with the top surface of the tray. When vacuum is released from the chamber, the fluid samples are loaded into the cards from the receptacles. A test card transport station transports the test cards from an incubation station to an optical reading station, where transmittance and fluorescence optical testing is conducted.
- U.S. Pat. No. 5,922,593 discloses a microbiological test panel assembly used in microorganism identification (ID) and antimicrobial susceptibility determinations (AST) testing is provided. The microbiological test panel assembly includes a plurality of test wells segregated into two sections. The test wells of each section are adapted to receive reagents capable of causing reactions used in performing ID and AST testing. The reagents enter the respective sections through fill ports and flow down a passageway of the test panel assembly in a serpentine manner filling all the test wells.
- U.S. Pat. No. 5,888,455 discloses an analyzer having a sample card transport station that moves a test sample card from an incubation station to a transmittance and fluorescence optical station. The transport station has a drive belt and an associated stepper motor to move the card to the optical stations. The fluorescence station has a linear flash lamp that illuminates a column of the wells of the cards simultaneously. A reference detector and dichromatic beam splitter are used to ensure that the fluorescence measurements are independent of lamp output changes over time.
- U.S. Pat. No. 5,863,754 discloses a process for bacteria identification and for determining the sensitivity of bacteria to antibiotics, and an apparatus and measuring supports for carrying out this process. A given volume of bacterial colony is introduced into a primary receiver and is dispersed within a liquid to form a precalibrated inoculum. This inoculum is moved between the primary receiver and one or more measuring supports so that the transferred quantities of bacteria correspond to the quantities required for the analyses to be carried out. Measurements are taken on the content of the compartments during or at the end of one or more incubations and are processed in order to characterize the growth of the bacteria present in the inoculum, to identify them and/or to determine their sensitivity to various antibiotics.
- U.S. Pat. No. 5,807,523 discloses an automatic chemistry analyzer using nephelometric and turbimetric analyzers to analyze parameters within liquid samples in a medical testing laboratory. The analysis machine also includes an onboard control sample so that the machine can be programmed to periodically calibrate its analyzing equipment during the course of normal operation. The machine also includes a sample station carousel having retainer clips for retaining a sample container rack which is constructed to retain a bar-coded card containing information regarding reagents used in the machine. A bar code reader located proximate to the sample carousel reads the bar-coded reagent information into the controller.
- U.S. Pat. No. 5,762,873 discloses an automatic sample testing machine for testing samples stored in test cards. The machine has a test sample positioning system for moving a tray containing a plurality of test sample cards and fluid receptacles among various stations in the machine. The machine has a diluting station for adding a predetermined quantity of diluent to the receptacles as needed. A pipetting station transfers fluid from one receptacle to another. A vacuum station is provided having a vacuum chamber moveable relative to the tray between upper and lower positions. The chamber cooperates with the tray to make a sealing engagement with the top surface of the tray when it is lowered to the lower position. A vacuum generator supplies vacuum to the chamber. When the vacuum is released from the chamber, the fluid samples are loaded into the cards from the receptacles. The test sample positioning system moves the tray to a cutting and sealing station and then to an incubation station and loads the cards one at a time into a carousel within the incubation station. A test card transport station transports the test cards from the incubation station to an optical reading station, where optical measurements are conducted on the wells of the card. When the card has been read, it is either moved back to the incubation station for additional incubation and reading or transferred to a card disposal system.
- U.S. Pat. No. 5,670,375 discloses a sample card transport station which moves a test sample card from an incubation station to a transmittance and fluorescence optical station in a sample testing machine. The sample card transport station has a drive belt and an associated stepper motor. The belt supports the card from one side of the card. A ledge having a card slot is disposed above the belt. The card is snugly received within the card slot, and supported from below by the drive belt and rollers for the belt. When the motor turns the belt, the belt grips the card and slides the card along the slot to the optical stations, without slippage between the belt and the card.
- U.S. Pat. No. 5,627,041 discloses a rotary cartridge adapted to present a biological sample to an imaging instrument for analysis by. The cartridge utilizes a series of channels, capillaries, reservoirs and stop junctions to move a sample, reagent and diluent through the cartridge as a function of the sum of capillary, gravitational and low centrifugal forces acting thereon.
- U.S. Pat. No. 5,266,268 discloses a multi-well rotor which reduces tendencies of reagent or sample materials to spontaneously move or “wick” from one chamber compartment to another, resulting in premature co-mingling of reactants, and of sample or reagent material to flow out of one or more of the outer loading ports during acceleration of the rotor for transfer of the sample or reagent material from inner chambers to corresponding outer chambers.
- U.S. Pat. No. 4,676,951 discloses an automatic system for analyzing microbiological specimens which have been treated and arranged in a plurality of specimen trays with each tray containing a plurality of specimens. Tray towers support a plurality of specimen trays. A work station selectively moves the trays one at a time from the tower to selectively deliver reagent or analyze the specimen in the tray. A control system is adapted to sequentially actuate the work station to properly sequence the system so that the reagents are administered to the respective specimen and the specimen is analyzed after a desired incubating period.
- U.S. Pat. No. 4,448,534 discloses an apparatus for automatically scanning electronically each well of a multi-well tray containing liquid samples. A light beam is passed through the wells to an array of photosensitive cells, one for each well. There is also a calibrating or comparison cell for receiving the light beam. An electronic apparatus reads each cell in sequence, completing the scan without physical movement of any parts. The resultant signals are compared with the signal from the comparison cell and with other signals or stored data and determinations are made and displayed or printed out.
- From this discussion of the art state in automated microbiological analyzers, it may be seen that current microbiological analyzers frequently employ multiple-well test panels capable of performing ID and AST testing on the same or separate different test panels. In particular, in the analyzer described in the family of patents related to U.S. Pat. No. 5,762,873 discussed above, prior to the start of a testing procedure, a technician loads a cassette with a plurality of test cards wherein the test cards come in two varieties: (1) identification cards, in which particular different growth media are placed in each of the wells of the card when the cards are manufactured, and (2) susceptibility cards, in which different concentrations of different antibiotics are placed in each of the wells of the card. In the analyzer described in U.S. Pat. No. 6,096,272, discussed above, a technician must inoculate a combination ID/AST test panel with an unknown microorganism and then place that panel into the analyzer where it is then incubated and analyzed periodically. From this it may be seen that prior to the use of the automated features of such state-of-the art microbiological analyzers, an operator is required to select the particular ID and/or AST test cards or devices that are required to perform the analyses called for by a physician and then either: (1) to inoculate and load the selected ID and/or AST test cards onto the analyzer, or (2) to load the selected ID and/or AST test cards onto the analyzer where the cards are automatically inoculated with test sample.
- Hence, state-of-art analyzers require an operator to manually select test panels or rotors already preloaded with the particular substrates, growth media, reagents, etc., required to perform the ID and/or AST determinations that have been ordered by a physician from a hospital's supply resources and load them by hand onto an analyzer. Preloaded panels and rotors typically also include test wells with substrates, growth media, reagents for ID and/or AST determinations that have not been ordered by a physician, thereby introducing unnecessary waste. Thus, known analyzers do not provide the flexibility needed to provide a microbiological analyzer that is adapted to automatically select from an on-board inventory of test devices pre-loaded only with the substrates, growth media and/or reagents as required to perform only those specific ID and AST determinations ordered by a physician. There is thus an unmet need for a fully automated, high throughput microbiological analyzer having such capabilities flexibility built into the analyzer in order to minimize waste and operator involvement.
- The present invention meets the foregoing needs by providing a fully automated random access microbiological test analyzer having the capability to select from among an inventory of different AST test arrays adapted for performing different AST tests, from among an inventory of broth containers adapted to provide different growth media as required for performing the different AST tests, and from among an inventory of different ID test rotors adapted for performing different ID tests and having the capability to also perform the desired ID and AST testing. Incoming patient samples to be tested are bar-coded with identifying indicia from which the ID and AST tests that are desired to be performed by the analyzer may be determined by a computer programmed to appropriately operate the analyzer. An exemplary embodiment of the present invention is directed at a microbiological analyzer having a plurality of different AST test arrays housed in different rectangular AST canisters and the AST canisters are maintained on a first rotatable carousel. The different AST test arrays are preloaded with increasing concentrations of a number of different antibiotics, or antimicrobial agents. The analyzer is programmed to automatically select the numbers of different AST test arrays required to complete the requested AST protocols and load the AST test arrays onto an appropriate carrier for transportation to various incubation and testing stations. A plurality of different broth containers are housed in different tube-like broth canisters and the broth canisters are also maintained on the second rotatable carousel. The different broth containers are preloaded with a number of different broth solutions. Depending on the details of a particular AST testing protocol, the requisite broth containers are selected automatically by the analyzer, diluted with sample inoculum and mixed. An appropriate amount of inoculum-broth solution is then placed into each AST test device after the AST test devices have been loaded onto the AST carrier for transportation throughout the analyzer. The analyzer similarly has a plurality of different ID test rotors housed in different tube-like ID canister and the ID canisters are maintained on a second rotatable carousel. The different ID test rotors are preloaded with substrates and reagents that are selected to produce a known pattern of measurable reaction signals that correspond to various known microorganisms. The analyzer is programmed to automatically select the numbers of different ID test rotors required to complete the requested ID protocols and to load the ID test rotors onto an appropriate carrier for transportation to requisite sample loading, incubation and analysis stations with minimal clinician attention. In addition, the analyzer employs a high-speed, compact, in-line sample pipetting and delivery system that aspirates sample from open sample tubes and deposits sample aliquots as required into ID test rotors and broth containers and that also aspirates sample-broth mixtures from broth containers and places such mixtures into AST test arrays.
- These and other features and advantages of the present invention can best be understood by reference to the detailed description of the preferred embodiments set forth below taken with the drawings in which:
- FIG. 1 is a simplified schematic plan view of an automated microbiological analyzer illustrative of the present invention;
- FIG. 2 is a simplified schematic elevation view of the automated microbiological analyzer of FIG. 1;
- FIG. 3 is an simplified schematic plan view of a sample pipetting and delivery system useful within the analyzer of FIG. 1;
- FIG. 4 is a perspective view of the pipetting and delivery system of FIG. 3;
- FIG. 5 is a top view of an AST test array useful within the present invention;
- FIGS. 5A and 5B are cross-section views of the AST test array of FIG. 5;
- FIG. 5C is a top view of an alternate AST test array useful within the present invention;
- FIGS. 5D and 5E are cross-section views of the AST test array of FIG. 5C;
- FIG. 6 is a bottom view of the AST test array of FIG. 5C;
- FIG. 6A is a bottom view of an AST test array useful within the present invention;
- FIG. 7 is a perspective view of an AST test array canister useful within the present invention;
- FIG. 7A is an enlarged side elevation view of the AST test array canister of FIG. 7;
- FIG. 7B is a sectional view of the AST test array canister of FIG. 7;
- FIG. 8 is a top view of an ID test rotor useful within the present invention;
- FIGS. 8A and 8B are cross-section views of the ID test rotor of FIG. 8;
- FIG. 8C is a top view of a first alternate ID test rotor useful within the present invention;
- FIG. 8D is a cross-section view of an second alternate ID test rotor useful within the present invention;
- FIG. 8E is a cross-section view of a third alternate ID test rotor useful within the present invention;
- FIG. 9 is a perspective bottom view of the ID test rotor of FIG. 8 useful within the present invention;
- FIG. 10 is a perspective view of an ID canister useful within the present invention;
- FIG. 10A is an enlarged perspective front view of the ID canister of FIG. 10;
- FIG. 10B is an enlarged perspective back view of the ID canister of FIG. 10;
- FIG. 10C is a cross-sectional view of the ID canister of FIG. 10;
- FIGS.11A-11D are various views of a broth container useful within the present invention;
- FIGS. 12A and 12B are perspective views of the broth container of FIG. 11;
- FIG. 13 is a schematic elevation view of a vortex mixer useful within the present invention;
- FIG. 14 is a perspective view of a broth canister useful within the present invention;
- FIG. 14A is an enlarged perspective view of the broth canister of FIG. 14;
- FIG. 14B is a sectional view of the broth canister of FIG. 14;
- FIGS.15A-M illustrate the functions of the sample pipetting and transport system of FIG. 3 in filling the AST test arrays of FIG. 5;
- FIG. 16 is a side elevation view of an ID rotor robotic device useful within the present invention;
- FIG. 17 is a perspective view of an AST array carrier useful within the present invention;
- FIG. 18 is a perspective view of an AST carrier transport useful within the present invention;
- FIG. 18A is a perspective view of the AST array carrier of FIG. 17 nested within a AST carrier transport of FIG. 18 useful within the present invention;
- FIG. 19 is a top plan view of an AST array dispenser useful within the present invention;
- FIG. 20 is a view of an AST carrier transport useful within the present invention;
- FIG. 21 is a view of an broth container handling apparatus useful within the present invention;
- FIGS. 21A and 21B are enlarged views of a portion of the broth container handling apparatus of FIG. 21;
- FIG. 22 is a view of an ID rotor filling and centrifuge device useful within the present invention;
- FIG. 23 is a side elevation view of a pipetting apparatus useful within the present invention; and,
- FIG. 24 is illustrative of a liquid sample filling process using the AST test array of FIG. 5.
- FIG. 1 schematically illustrates an embodiment of the automated random access
microbiological analyzer 10 of the present invention, theanalyzer 10 having an on-board inventory ofAST test arrays 12 adapted for performing different AST tests, a plurality of broth containers 14 (also seen in FIG. 2) adapted to provide different growth media as may be required for AST testing, and a plurality ofID test rotors 16 adapted for performing different ID tests. The term “random access” indicates the ability to randomly select any number of differentAST test arrays 12,different broth containers 14, and differentID test rotors 16 as required for microbiological testing. The inventory of differentAST test arrays 12 are maintained withinanalyzer 10 in different rectangularity elongate ASTtest array canisters 18. TheAST canisters 18 are attached to arotatable post 20, hereinafter called theAST canister post 20; theAST canister post 20, ASTcanisters 18 andAST test arrays 12 are housed within an environmentally controlled AST inventory chamber 22 (top portion is removed for purposes of illustration in FIG. 1). The differentAST test arrays 12 are preloaded with increasing concentrations of a number of different antibiotics, or antimicrobial agents as required, to perform AST testing on a patient sample, also called inoculum herein, as requested by a physician. In FIG. 2, theAST inventory chamber 22 is shown with afirst door 23 or seal 23 provided to allow operating access to any one of theAST canisters 18 when ASTcanisters 18 are rotated byAST canister post 20 into alignment with anAST array dispenser 84 described later. TheAST inventory chamber 22 also has asecond door 27 to allow theAST canisters 18 to be mounted ontoAST canister post 20 by an operator. In a exemplary embodiment, as many as seventy-fiveAST test arrays 12 would be contained within eachAST canister 18, described later in FIG. 7, and as many as seventy-fiveAST canisters 18 would be housed within theAST inventory chamber 22. - The plurality of different broth cups or containers14 (FIG. 2, left side) are maintained in an on-board inventory within
analyzer 10 in different tube-like broth canisters 24, FIG. 14, and thebroth canisters 24 are maintained on arotatable carousel 26, hereinafter called the B/ID carousel 26, the B/ID carousel 26 being housed within an environmentally controlled B/ID chamber 28 (shown with its top portion removed for purposes of illustration). A rotating motor is operated as required to rotate the B/ID carousel 26 so as to present a requiredbroth canister 24 andbroth container 14 to a broth container handling device described later. Thedifferent broth containers 14 are preloaded with a number of different standard broth solutions that act as a growth media during AST testing. In FIG. 2, the B/ID chamber 28 is shown with adoor 30 in an opened position to allow operating access to the inside of the B/ID chamber 28. Thebroth canisters 24 are shown as being made of a transparent material or as cut-away in order to shown fourbroth containers 14 contained within thebroth canisters 24. In a exemplary embodiment, as many as twentybroth containers 14 would be contained within eachbroth canister 24 and as many as fourteenbroth canisters 24 would be housed within the B/ID chamber 28. An important feature ofanalyzer 10 is a magnetic mixing member within eachbroth container 14 and an associatedvortex mixer 93, both described later, provided so as to properly mix patient sample disposed intobroth containers 14 with broth solution contained withinbroth containers 14. - In a similar manner, the
analyzer 10 has an on-board inventory of differentID test rotors 16 described hereinafter, FIG. 8, that are maintained in an inventory withinanalyzer 10 in different tube-like ID canisters 32, FIG. 10, and theID canisters 32 are maintained along withbroth canisters 24 on the B/ID carousel 26 within B/ID chamber 28. The differentID test rotors 16 are preloaded with substrates and reagents that are selected to produce a known pattern of measurable reaction signals which correspond to various known microorganisms.Motor 25 is also operated as required to rotate the B/ID carousel 26 so as to present a requiredID canister 32 andID test rotor 16 to a rotor handling device described later. In an exemplary embodiment, as many as eightyID test rotors 16 would be contained within eachID canister 32 and as many as fourID canisters 32 would be housed upon the B/ID carousel 26. - Patient samples are presented to the
analyzer 10 inopen sample tubes 34 placed in openings in a number ofsample tube holders 36 located near the periphery of a rotatable circular tray, known hereinafter as S/PT tray 38, rotatable by a S/PT tray motor 44.Sample tube holders 36 are generally curved, each forming a sector of the circumference of a circle. Four of suchsample tube holders 36 are seen in FIG. 1 supported onrotatable tray 38, however any number ofsample tube holders 36 may be sized and adapted to fit onto thecircular tray 38. Conventional bar-code readers 35 are placed proximatesample tube holders 36 so as to determine the identity ofsample tubes 34 and aturbidity reader 37 is similarly placed so as to confirm that the concentration of microbiological organisms withinsample tubes 34 is within a predetermined range of acceptable values. An important feature ofanalyzer 10 is a magnetic mixing member within eachsample tube 34 and an associatedvortex mixer 93, both described later, provided so as to properly mix patient sample contained insample tubes 34 beforeturbidity reader 37 is employed. A sensor (not shown) to detect the presence of magnetic mixing member within eachsample tube 34 is optionally provided proximate S/PT tray 38 to ensure the presence of such a magnetic mixing member. Asample dilution station 97 is also located proximate S/PT tray 38 and is adapted to dilute sample contained insample tubes 34 if the concentration of microorganisms in sample liquid carried withintubes 34 is determined byturbidity reader 37 to be higher than an allowable range. - The S/
PT tray 38 also supports a number ofpipette tip holders 40 located in the innermost portion of S/PT tray 38.Pipette tip holders 40 are generally elongate and may have a curved shape and eachpipette tip holder 40 is adapted to hold a plurality ofdisposable pipette tips 42. Six of suchpipette tip holders 40 are seen in FIG. 1, however any number ofpipette tip holders 40 may be sized and adapted to fit onto the S/PT tray 38. The S/PT tray 38 may be rotated bymotor 44 so as to present any of thepipette tips 42 and any of theopen sample tubes 34 to apipetting apparatus 46. Thepipetting apparatus 46 is adapted to remove one of thepipette tips 42 frompipette tip holder 40, to insert thepipette tip 42 into anopen sample tube 34, and to aspirate a known amount of patient sample from thesample tube 34 into thepipette tip 42. Thepipetting apparatus 46 is further adapted to dispense a known amount of patient sample frompipette tip 42 into abroth container 14 orID test rotor 16, as described hereinafter. - S/
PT tray 38,pipetting apparatus 46, B/ID chamber 28, ASTinventory chamber 22, and ID incubation andtesting chamber 48 are supported above anupper operating plate 11 that provides a first operating plane foranalyzer 10. Alower base plate 13, typically mounted on rollers, provides a second operating plane for additional structure foranalyzer 10. -
Analyzer 10 comprises two separate incubation and analysis chambers as required for ID and AST testing. An ID incubation andanalysis chamber 48 is seen in the top plan schematic view of FIG. 1 with its uppermost surface removed to expose an interior portion in which an IDrobotic device 50, also seen in FIG. 16, is adapted to remove differentID test rotors 16 fromID canisters 32 and to then move theID test rotors 16 to and from an ID rotor filling and centrifugingapparatus 52, described later, moveable between theID incubation chamber 48 and a sample pipetting anddelivery system 60 described hereinafter and illustrated in FIG. 3. IDrobotic device 50 comprises arobotic arm 54 that carries a gear-drivenmechanism 56 that activates a pair of claw-like gripping pincer-teeth 58 at an end ofarm 54. Pincer-teeth 58 are sized and spaced to grip grippingtroughs rotor 16, described hereinafter, thereby to move alowermost ID rotor 16 fromID canister 32 to centrifugingapparatus 52 when centrifugingapparatus 52 is positioned within the ID incubation andanalysis chamber 48. A vertically translatablerotation motor system 64 provides vertical and rotational motion torobotic arm 54 so thatID rotors 16 may positioned throughout all of the interior of incubation andanalysis chamber 48. Devices that perform the functions ofrobotic device 50 are well known in the art as computer-controlled pick-and-place robotic devices. - In FIG. 2, an AST incubation and
analysis chamber 70 is seen located below the operatingplate 11 with a firstside surface portion 71 opened to reveal an interior section in which a number of rotatable AST incubation racks 72 support a number ofAST carriers 74, FIG. 17, theAST carriers 74 being adapted as described hereinafter to hold a number ofAST test arrays 12 as they are transported throughoutanalyzer 10. AnAST carrier transporter 76, FIG. 18, is mounted on a vertically orientedAST transport rod 83 and is adapted to be moveable from above theupper operating plate 11 to above thelower base plate 13. TheAST carrier transporter 76 is shown in uppermost and lowermost positions in FIG. 2 for purposes of explanation even though there is only one suchAST carrier transporter 76. In the uppermost position above the operatingplate 11, as best seen in FIG. 1, theAST carrier transporter 76 can access anAST array carrier 74 transported on anAST carrier transport 78 described hereinafter and lower theAST array carrier 74 through anAST transport opening 81 in the operatingplate 11. In the lowermost position,AST carrier transporter 76 is adapted to deposit anAST array carrier 74 into an ASTvacuum filling station 82 positioned on thelower base plate 13 and described hereinafter. For purposes of simplicity in illustration,chambers analysis chamber 70 and ID incubation andanalysis chamber 48 share a common environmentally controlled space with the only opening to the external environment being betweenAST carrier transporter 76 and anAST array dispenser 84 described later. - The
AST carrier transporter 76 is further adapted to be vertically moveable from between thevacuum filling station 82 on thelower base plate 13 and the uppermostAST incubation ledge 73 within AST incubation andanalysis chamber 70. TheAST carrier transporter 76 is further adapted to remove anAST array carrier 74 from thevacuum filling station 82 and to deposit theAST array carrier 74 on any one of the pairs ofAST incubation ledges 73 within any of the AST incubation racks 72 inside AST incubation andanalysis chamber 70. A openedsecond side portion 79 is formed in the exterior wall of the AST incubation andanalysis chamber 70 to facilitate transfer from theAST carrier transporter 76 to the AST incubation racks 72. - An
AST array dispenser 84 is seen in FIG. 1 as being disposed between theAST chamber 22 andAST array carrier 74. TheAST array dispenser 84 is adapted to remove aAST test arrays 12 from ASTcanisters 18 in the form of a singulated stream and to successively place theAST array 12 within emptyAST array slots 86 formed within an AST array carrier 74 (FIG. 17).AST array dispenser 84, FIG. 19, comprises an ejection means 368 operable with an alignment means 360 and a biasing means 362 to precisely align and eject the lowermostAST test array 12 from any one of the vertically orientedAST canisters 18 into an emptyparallel slot 86 whenslot 86 is aligned byAST carrier transport 78 with the elongate dimension of a firstAST test array 12 having therein the antibiotics as required to perform a first AST test ordered by a physician. Subsequent to loading of the firstAST test array 12 into the firstparallel slot 86, ASTcarrier transport 78 indexes theAST array carrier 74 step-wise relative to theAST array dispenser 84 so as to align a second emptyparallel slot 86 inAST array carrier 74 with asecond AST canister 18 containing theAST test arrays 12 having therein the antibiotics as required to perform a second AST test ordered by a physician. As described previously, a plurality of differentAST test arrays 12 are maintained withinanalyzer 10 indifferent AST canisters 18 attached to a rotatableAST canister post 20. Simultaneously with theAST array carrier 74 being moved relative to theAST array dispenser 84, theAST canister post 20 is rotated to present toAST array dispenser 84 another of theAST canisters 18 housing the particularAST test arrays 12 preloaded with the appropriate antibiotics required to perform another AST test ordered by a physician. -
AST array dispenser 84 is then operated to push the lowermostAST test array 12 withinsecond canister 18 into the second emptyparallel slot 86 inAST array carrier 74.AST array dispenser 84 continues this operation in conjunction with rotation of AST canister post until the number of differentAST test arrays 12 as are required to perform all of the different AST tests ordered by a physician have been loaded ontoAST carriers 74.AST carrier transport 78 comprises a translatable belt, lead-screw or similar mechanism as illustrated in FIG. 20 adapted to securely support and moveAST carrier beds 80 supporting ASTcarriers 74 as described later over the operatingplate 11 in a linear path below pipettingapparatus 46. Incoming patient samples are bar-coded with identifying indicia from which the AST tests that are desired to be accomplished may be established byCPU 15.Analyzer 10 of the present invention thus provides random access to any one of a number of different AST tests because of the inventory of differentAST test arrays 12 contained withindifferent AST canisters 18 housed within theAST chamber 22. - In an exemplary embodiment, as many as ten AST incubation racks72 may be contained within the AST incubation and
analysis chamber 70 and as many as twenty ASTcarriers 74 may be supported on pairs ofledges 73 in eachAST incubation rack 72. The uppermost pair of ledges is reserved for usedAST carriers 74 to be transferred to a disposal (not shown). AnAST array reader 90 is positioned withinAST incubation chamber 70 proximate the periphery of the AST incubation racks 72 and is adapted to remove a singleAST array carrier 74 from anAST incubation rack 72 and to perform AST optical analysis on samples contained within theAST test arrays 12 carried byAST array carrier 74. After AST optical analysis is completed,AST array reader 90 is similarly adapted to return theAST array carrier 74 to its original position within theAST incubation rack 72. TheAST reader 90 is mounted on a pair of vertically orientedshafts 92 and is moveable between the next-uppermost and lowermostAST array carrier 74 withinAST incubation chamber 70 so that allAST carriers 74 within AST incubation andanalysis chamber 70 may be removed from all AST incubation racks 72 for testing. EachAST incubation rack 72 is attached to arotatable platen 91 so that allAST carriers 74 may be presented as required for optical analysis to theAST reader 90. - U.S. Pat. No. 4,448,534, assigned to the assignee of the present invention, describes a scanning apparatus for performing optical density tests on liquid samples that is typical of the
AST reader 90 used inanalyzer 10. The apparatus of the prior patent includes an optical testing system for automatically electronically scanning each well of a multi-well test device containing several different liquid samples. Two beams of interrogating radiation from are passed through a plurality of AST test wells arrayed in two concentric circles as described later to an opposing array of photosensitive cells, one photosensitive cell for each test well. The intensity of the beam of interrogating radiation may be monitored and the associated power source adjusted using feed-back mechanisms so as to maintain a stable intensity level. There is optionally also provided a calibrating or comparison test well for receiving the radiation. Electronic apparatus read the optical signals emanating from each test well in sequence completing a scan of all test wells in the array as the test array is passed between the radiation source and the array of photosensitive cells. The resultant signals are compared with the signals from a comparison cell and with other signals or stored data, and AST determinations are made and then recorded withinCPU 15 and displayed or printed out. A system of the type described above is similar to that sold under the trademarks WalkAway® analyzer by Dade Behring Inc., Deerfield, Ill. - As seen in FIG. 17, AST
array carrier 74 is formed with a number of individual parallelopen slots 86, eachslot 86 having an elongate optical reader opening 94 formed in thecarrier base 75 of thecarrier 74 to facilitate optical measurements as described above.Reader openings 94 are sized and shaped so as to allow the interrogating beam of radiation to be passed through the plurality of microwells in aAST test array 12 described hereinafter.AST array carrier 74 further includes anotch 96 and chamferededges 101 formed in thebase 75 ofcarrier 74 and a pair of chamferededges 98 formed in a raisedflange 100 to facilitate secure transportation of theAST array carrier 74 throughoutanalyzer 10. Additionally, these features, notch 96 and chamferededges carrier 74 for optical analysis by a biasing means atnotch 96 adapted to urge thecarrier 74 against a stop mated with the raisedflange 100.Slots 86 are defined by a number ofrails 87 extending upwardly fromcarrier base 75 andsuch rails 87 serve to maintainAST test arrays 12 in a stable and secure position withinAST array carrier 74. An important feature ofAST array carrier 74 is ahandle 99 formed inbase 75 to facilitate movement ofAST array carrier 74 to and fromAST carrier bed 80, to and fromAST carrier transporter 76, to and fromAST incubation rack 72, to and fromoptical reader 90, to and from an ASTvacuum filling station 82, and to and from an AST disposal station (not shown). FIG. 17 shows a typical arrangement of the various features onAST array carrier 74 that cooperate with ASTcarrier transport system 78 andAST carrier transporter 76 as thecarriers 74 are securely and automatically moved withinanalyzer 10 in response to commands fromCPU 15.AST carrier transporter 76 comprises a claw-like arm operated byCPU 15 so as to grasp anAST array carrier 74 usinghandle 99 and move theAST array carrier 74 withinanalyzer 10 as described above. - FIG. 18 shows AST
carrier bed 80 comprising a generally flat ASTcarrier transport base 350 sized to accept anAST array carrier 74 between a fixed ASTcarrier registration wall 352 and an AST carriertransport bias wall 354. AST carriertransport bias wall 354 supports a spring-loadedAST carrier detent 356 positioned to mate againstnotch 96 formed in thebase 75 ofAST array carrier 74 thereby to urgeAST array carrier 74 securely against ASTcarrier registration wall 352. An AST carrier transportside wall groove 358 is formed in AST carriertransport bias wall 354 to enhance the security ofAST array carrier 74 withinAST carrier bed 80. FIG. 18A shows such anAST array carrier 74 nested withinAST carrier bed 80 and retained therein byAST carrier detent 356. - An important feature of the
analyzer 10 is a multi-functional sample pipetting anddelivery system 60 illustrated schematically in FIG. 3 in which only some of the features and elements ofanalyzer 10 are depicted for the sake of simplicity. Sample pipetting anddelivery system 60 is adapted to remove apipette tip 42 from apipette tip holder 40 using apipetting apparatus 46, aspirate a known quantity of liquid sample from anopen sample tube 34 held in asample tube holder 36 and to deposit a portion of or all of the aspirated sample into either of, or both of, abroth container 14 or anID test rotor 16.Pipetting apparatus 46 is supported on a raised frame 102 (FIG. 4) and is adapted to be moved typically by astepper motor 104 and lead screw 106 (FIG. 3) as controlled byCPU 15 between: - 1. a first position, identified as46 a, for accessing
pipette tips 42; - 2. a second position, identified as46 b, for aspirating sample from
sample tube 34; - 3. a third position, identified as46 c, for depositing a known amount of sample into a
broth container 14 and subsequently aspirating a known amount of mixed sample-broth solution frombroth container 14; - 4. a fourth position, identified as46 d, for depositing a known amount of mixed sample and broth into an
AST test array 12; - 5. and a fifth position, identified as46 e, for depositing a known amount of sample into an
ID test rotor 16. - Sample pipetting and
delivery system 60 is adapted to be moved in two opposed directions along a linear path defined by the loci L ofpositions analyzer 10 simplifies movement ofpipetting apparatus 46 betweenpipette tips 42 inpipette tip holder 40,sample tubes 34 insample tube holder 36,broth containers 14, ASTtest arrays 12 within ASTarray carrier 74, andID rotors 16 within filling and centrifugingapparatus 52.Positions position 46 d is a multiple number of locations whereat sample-broth solution is dispensed into a reservoir withinAST arrays 12 to fill thearrays 12. The linear movement ofpipetting apparatus 46 between operating position along loci L, the changing location ofposition 46 d during AST array filling, taken in conjunction with anAST carrier 74 “build and fill” process described later advantageously reduces the amount of idle time needed for ID and AST testing byanalyzer 10, thereby increasing throughput ofanalyzer 10. - FIG. 4 is a perspective view of the multi-functional liquid sample pipetting and
delivery system 60 and shows the positional relationships betweenpipette tips 42 shown inposition 46 a,sample tubes 34 shown inposition 46 b,broth containers 14 shown inposition 46 c,AST array containers 74 shown inposition 46 d, anID rotor 16 shown inposition 46 e. - The sample pipetting and
delivery system 60 further comprises the previously mentionedpipetting apparatus 46, a brothcontainer handling apparatus 108 seen in FIG. 21 and adapted to remove abroth container 14 from the B/ID carousel 28 and to present thebroth container 14 to thepipetting apparatus 46, and an ID rotor filling and centrifugingapparatus 52 seen in FIG. 22 and adapted to remove anID test rotor 16 from the ID incubation andanalysis chamber 48 and presentID test rotor 16 to thepipetting apparatus 46. ID rotor filling andcentrifuge device 52 is further adapted to replace anID test rotor 16 back into theID incubation chamber 48 after presentation to thepipetting apparatus 46. The ID rotor filling andcentrifuge device 52 is even further adapted to centrifugally rotate anID test rotor 16 so as to distribute sample deposited therein by thepipetting apparatus 46. - In conjunction with the ID rotor filling and
centrifuge device 52, the brothcontainer handling apparatus 108, rotatable S/PT tray 38,ID rotors 16 and ASTarrays 12, sample pipetting anddelivery system 60 is able to automatically provide rapid and random access withinanalyzer 10 to all patient samples to be tested for ID and AST characteristics, to all reagents necessary to perform such ID and AST tests, and to all sample handling or test devices necessary for such ID and AST tests, without requiring operator intervention. - Devices adapted to perform the functions of
pipetting apparatus 46, FIG. 23, are generally known and typically include stepper motor 104 (FIG. 3) andlead screw 106, a vacuum operated liquid sample aspiration/disposition system 114, and a verticallinear drive 116 having a taperedpipette tip mandrel 118 at its lower extremity, themandrel 118 being sized for an interference fit into apipette tip 42.Stepper motor 104 andlead screw 106 provide linear movement of thepipetting apparatus 46 along the path defined bypositions Linear drive 116 provides vertical movement to apipette tip 42 thereby to access the various liquid containers previously described.Pipetting apparatus 46 thereby provides means for aspiration of patient sample from asample tube 34 and deposition of said sample into either of, or all of, abroth container 14, anID rotor 16, and aspiration of mixed sample-broth solution from abroth container 14 and dispensing into anAST test array 12 carried by anAST carrier 74. - FIG. 5 shows the upper
top surface 120 of anAST array 12 as containing relatively structured features described hereinafter and FIG. 6 shows thelower bottom surface 122 of anAST array 12 as being relatively flat. As described in a co-pending U.S. patent application Ser. No.______/______, eachAST array 12 has an elongate length and a plurality of upwardly projecting AST microwells 124 formed in thebottom surface 120 as a linear row ofsingle microwells 124 parallel to the length of thearray 12.Top surface 120 andbottom surface 122 are on opposing surfaces and are separated by anindented sidewall 126 and anopposed sidewall 128. Asacrificial evaporation well 132 is formed in thebottom surface 122 of the test array upwardly projecting from an open portion of thebottom surface 122 and disposed between the row ofmicrowells 124 and areservoir 134 and is connected by afirst microchannel 130 to thereservoir 134. Evaporation well 132 has a closed dome-shapedupper well surface 136 proximate thetop surface 120 of the test array with asealable vacuum port 138 formed therein as an opening in the dome-shapedupper well surface 136 of the evaporation well 132, as seen in FIG. 5A depicting a cross-section view along lines A-A of FIG. 5.Microwells 124 have the general shape of a closed well projecting upwards from thebottom surface 122 of thearray 12 with a depth of about three-fourths the thickness ofarray 12, as seen in FIG. 5B depicting a cross-section view along lines B-B of FIG. 5, and have their openings along thebottom surface 122 ofarray 12. - As seen in FIG. 6,
first microchannel 130 is formed as a open groove in thebottom surface 122 of thearray 12 and connects the evaporation well 132 to a open top rectangular shaped inoculum-brothsolution receiving reservoir 134 best seen in FIG. 5, thereservoir 134 having a closed bottom illustrated by dashed lines in FIG. 6. One end of the bottom of thereservoir 134 has a flow opening 140 also illustrated in FIG. 6 to allow inoculum-broth solution dispensed into the open top ofreservoir 134 to flow fromreservoir 134 throughfirst microchannel 130, firstly into the sacrificial evaporation well 132 and therefrom to asecond microchannel 142 and therefrom sequentially through a number of connectingmicrochannels 143 to each of the series ofmicrowells 124. The open surface portions of first andsecond microchannels microchannel 143, flow opening 140, sacrificial evaporation well 132, and microwells 124 along thebottom surface 120 ofarray 12 are closed by sealing over with a layer of adhesive film (not shown) during a manufacturing process in which antimicrobics of clinical interest are placed in thedifferent microwells 124 but not in thesacrificial evaporation well 132. Optionally, onemicrowell 124 may be left empty of antimicrobics for use in generating a reference signal during optical analysis. - Sacrificial evaporation well132 may be seen in cross-section in FIG. 5A as comprising a pair of mutually opposed
parallel endwalls 144 connected by a pair of mutually opposed parallel sidewalls 146 (only onesidewall 146 is visible in this view).Endwalls 144 are shorter thansidewalls 146; endwalls 144 andsidewalls 146 are substantially perpendicular to thebottom surface 122 oftest array 12. The upper surfaces ofendwalls 144 andsidewalls 146 are connected by the cone-shapedupper well surface 136 to form a small generallyrectangular evaporation chamber 148 enclosed bysacrificial well 132. An important feature ofsacrificial well 132 is thesealable vacuum port 138 formed as an opening in the cone-shapedupper surface 136 so that air may be evacuated fromsacrificial well 132,microchannels microchannel 143, and microwells 124 during an inoculum-broth filling operation described hereinafter.Evaporation chamber 148 is typically sized to accommodate an amount of inoculum-broth solution in the 0.02 to 0.04 mL range. - FIG. 5B illustrates the
microwells 124 as having atop surface 150 portion ofarray 12, arounded endwall portion 152 of theindented sidewall 126, aflat endwall 154 of theindented sidewall 126 and twoparallel sidewalls 156. Bothendwalls lower bottom surface 122 ofarray 12 and are separated by the twoparallel sidewalls 156. The irregulartop surface 150, theflat endwall portion 154, and therounded endwall portion 152 cooperate to define a smallAST reaction chamber 158. Thetop surface 150 is shaped to form a recessedtop edge portion 160 ofAST reaction chamber 158 that functions as abubble trap 160 for bubbles that may be generated when inoculum-broth solution is dispensed fromreservoir 134 tosacrificial well 132 andtest microwells 132. It has been discovered that when themicrowells 124 are shaped as described herein, and when connectingmicrochannel 143 is positioned on the opposite surface ofmicrowell 124 across from thebubble trap 160,bubble trap 160 is effective in capturing bubbles whenmicrowell 124 is comprised of a generally hydrophilic material, like styrene. It has been observed that with such an arrangement, as inoculum-broth solution flows intomicrowell 124, any air remaining withinmicrowell 124 is urged by the expanding inoculum-broth solution without leaving any entrapped air pockets in the critical upper central area of theAST reaction chamber 158. Such a filling is pictorially illustrated in FIG. 24. Thus, air is removed away from the central area of thetop surface 150 through which a beam of interrogating radiation may pass as described hereinafter without requiring bubble traps separate from theAST reaction chamber 158 or bubble traps with complex valve features. - In an exemplary embodiment, the upper
top surface 120 andlower bottom surface 122 are about 0.3-0.4 inches wide, theindented sidewall 126 is about 0.2-0.25 inches in height and the elongate dimension of thetest array 12 is about 2.5-3.0 inches in length. In such an embodiment, themicrochannel 42 would be sized with a width and depth of about 0.010 to 0.020 inches. Preferably, theAST test array 12 is constructed of a moldable plastic material like styrene, but other types of material can be used. Most preferably, the material used in constructingarray 12 is generally translucent, so as to allow uninterrupted transmission of light throughmicrowells 124 during AST testing in themicrobiological analyzer 10. AST testing may conveniently be accomplished by directing a beam of interrogating radiation from above or below eachAST array 12 through a uppercentral arc portion 157 of thetop surface 150 of eachmicrowell 124 and measuring the degree of absorption or change in color or generation of a fluorescent signal using a calorimetric or fluorometric photodetector located below or above eachmicrowell 124. For this reason, theupper center portion 157 of thetop surface 150 of everymicrowell 124 and thelower center portion 159 of thetop surface 150 of everymicrowell 124 are molded so as to have a surface finish smoothness equivalent to or more smooth than SPI #A-1 grade #3 diamond buff in order to minimize optical interference. - The
sacrificial evaporation well 132 is designed to accomplish two important purposes: firstly, provision of aevaporation chamber 148 from which sacrificial evaporation of inoculum-broth solutions may take place, thereby inhibiting evaporation of solution frommicrowells 124. Evaporation frommicrowells 124 is inhibited because evaporation initially must occur from withinshort microchannel 130 and then from thesacrificial evaporation chamber 148 before evaporation might occur fromlong microchannel 142 andmicrowells 124.Evaporation chamber 148 further provides thesealable vacuum port 138 through which air contained withinmicrowells 124 may be evacuated so that air withinmicrowells 124 does not bubble through broth in thereservoir 134 during evacuation and generate air bubbles within inoculum-broth solutions. After evacuation,vacuum port 138 is subsequently sealed so as to generate a flow of inoculum-broth solution fromreservoir 134 into themicrowells 124. - In an alternate embodiment of
AST array 12 illustrated in FIG. 5C showing the top view of anAST array 12, taken in conjunction with FIG. 6B, showing the bottom view of anAST array 12, sacrificial evaporation well 132 may be separated fromvacuum port 138 but connected thereto by amicrochannel 131. FIG. 5D is a cross-section view along lines D-D of FIG. 5C and shows such a separated arrangement of sacrificial evaporation well 132 andvacuum port 138 in an embodiment in whichvacuum port 138 is seen as disposed at the upper surface of aninclined portion 133 of theupper surface 122 ofAST array 12. In this embodiment,vacuum port 138 is in fluid communication with sacrificial evaporation well 132 thereservoir 134 and is adapted to be temporarily sealed by a stopper pressed thereon. Thus,vacuum port 138 is not sealed by a heating action but is alternately sealed by temporarily forcing aresilient stopper 135 over thevacuum port 138 to effectively sealvacuum port 138 against air flow during the aforedescribed vacuum filling process. This temporary sealing step is illustrated in FIG. 5E where amoveable stopper support 137 is shown as positioned by an actuator 139 so thatstopper 135 effectively sealsvacuum port 138 thereby to fillmicrowells 124 with inoculum-broth solution when vacuum is released. In a preferred embodiment,vacuum port 138 is placed as illustrated between sacrificial evaporation well 132 andreservoir 134. Alternate locations ofvacuum port 138, for example, between sacrificial evaporation well 132 andmicrowells 124, have not given satisfactory performance. Once the vacuum is released within the vacuum chamber andmicrowells 124 are filled with inoculum-broth solution, theresilient stopper 135 may be removed fromport 48. - As seen in FIG. 5,
array 12 further includes aprotrusion 162 formed in thesidewall 128, theprotrusion 162 being generally shaped as a bulge extending from the body of thearray 12 and formed in the uppermost portion of thesidewall 128. Theprotrusion 162 is used to facilitate loading and retention of anAST array 12 within theAST carrier 74 and in an exemplary embodiment has dimensions of about 0.26-0.30 mm extension outward from the body ofarray 12, about 3-4 mm length along the edge of thearray 12 and about 0.6-0.8 mm depth along the sidewall 17 of thearray 12. Alternately, a high friction material such as silica or an inert powder may be coated onto the side ofarray 12 in place ofprotrusion 162 to accomplish a similar function. - FIG. 7 is a side elevation view of an
elongate AST canister 18 having a generally rectangular cross-section with two AST canisterflat sides 270 and two AST canister narrow sides 284 (FIG. 7B), theflat side 270 being about 10 times greater in dimension than thenarrow side 284.AST canister 18 is sized to house a plurality ofAST test arrays 12 stacked one atop another (indicated by dashed lines in FIG. 7.) and maintained secure by pairs of AST canisterinternal ribs 286 extending along the elongate height of AST canister flat sides 270. Key features of theAST canister 18 include an AST canister cylindrical pivot 272 (best seen in FIG. 7A) shaped to seat into a mating dock withininventory chamber 22 to allow theAST canister 18 to be rotated using an AST canister handle 274 to a vertical position where an ASTcanister seating flange 276 fits into a vertical groove 21 (FIG. 1) inAST canister post 20. ASTcanister seating flange 276 extends the full length of an AST canisternarrow side 284 except for a small ASTcanister alignment key 278 andalignment notch 279 provided to confirm proper orientation ofAST canister 18 with a corresponding slot forkey 278 and stop fornotch 279 within thevertical groove 21 inAST canister post 20.AST canister 18 also comprises an ASTcanister eject port 280 formed in the AST canisternarrow side 284 proximate AST canistercylindrical pivot 272 and sized to allow the lowermostAST test array 12 within the plurality ofAST test arrays 12 stacked one atop another to be pushed out ofAST canister 18.AST test arrays 12 may be pushed out ofAST canister 18 using aplunger entering canister 18 through an ASTcanister plunger port 282 that is aligned with ASTcanister eject port 280 and is formed in the AST canisternarrow side 284 opposing ASTcanister eject port 280. A pair of inwardly projectingdimples 289 are formed in AST canisterflat sides 270 and extend into ASTcanister eject port 280 to retainAST test arrays 12 withinAST canister 18, preventing accidental dislodging of aAST test array 12 fromcanister 18 and also to preventAST test arrays 12 from being improperly inserted back intocanister 18. - FIG. 8 is a top plan view of the
ID test rotor 16 useful in the present invention and described in a co-pending U.S. patent application Ser. No.______/______.Rotor 16 comprises a rotorupper surface 170 and arotor bottom surface 172 seen in FIG. 9.ID test rotor 16 has a rotorcentral axis 171, a rotor diameter D, and a generally flat radialouter sidewall 174 connecting theupper surface 170 andbottom surface 172 at the diameter D of therotor 16. A recessed circularcentral portion 176 is recessed below theupper surface 170 ofrotor 16. A first plurality of downwardly projectingmicrowells 178 are formed in the upper surface and are distributed equidistant from one another in a first circular array located at a first distance from thecentral axis 171; a second plurality of downwardly projectingmicrowells 182 are also formed in theupper surface 170 and are distributed equidistant from one another in a second circular array, located at a second distance from the central axis, the second distance being larger than the first distance; a first plurality of downwardly projectingmicrochannels 180 are formed in the top surface and connect the recessedcentral portion 176 to the first plurality ofmicrowells 178; a second plurality of downwardly projectingmicrochannels 184 are formed in theupper surface 170 and connect the recessedcentral portion 176 to the second plurality ofmicrowells 182. The recessed circularcentral portion 176 is surrounded by a generallyinclined annulus portion 188. The plurality offirst microchannels 180 extends radially outwards from aradial wall 190 formed vertically at the outer periphery of aninclined annulus 188 extending outwards from recessedcentral portion 176 towards the first circular array of equally spacedmicrowells 178; the plurality of second equally spacedmicrochannels 184 also extends radially outwards from theradial wall 190 to the second circular array ofmicrowells 182. The length offirst microchannels 180 is generally about ½ to 2{fraction (/3)} the radial length ofsecond microchannels 184. The two arrays of equally spaced microwells 178 and 182 are an important feature ofrotor 16 since the two arrays allow for a greater number of test microwells that is typically possible with conventional centrifugal rotors having a single array of test wells equidistant from the center of the rotor. The first and second plurality of downwardly projectingmicrowells microchannels - FIG. 8A shows a key feature of
rotor 16 as a topradial trough 192 formed in the top surface and a bottomradial trough 194 formed in the bottom surface, the top 192 and bottom 194 troughs are vertically aligned with one another but are not intersected and are provided to facilitate handling of therotor 16 by IDrobotic device 50 and by ID rotor filling and centrifugingapparatus 52 described hereinafter. Another feature ofrotor 16 is a single throughopening 196 formed between the topradial trough 192 and the bottomradial trough 194 thus fully extending from the top surfaceupper surface 170 to thebottom surface 172 to facilitate radial positioning ofrotor 116 within an ID rotoroptical analyzer 230 described hereinafter. Optionally, asmall notch 198 may be formed insidewall 174 and made to fully extend from thetop surface 170 to thebottom surface 172 to facilitate reagent pre-loading ofmicrowells - FIG. 8C illustrates an alternate embodiment of the
ID test rotor 16 of the present invention in which a circular,thin layer 211 of tape stock is shown in dashed lines for clarity and has anopening 213, also shown in dashed lines, formed at its center and adhesively adhered to thetop surface 170 ofrotor 16. Tape stock layer 201 is positioned so that theopening 213 is aligned over the recessedcentral portion 176 of the rotor.Opening 213 is provided within thetape stock layer 211 to allow free access by an inoculum dispensing mechanism to an inoculum receiving chamber formed bysurface 176,inclined annulus portion 188,radial wall 190 andtape stock layer 211. Theopening 213 intape stock layer 211 generally has a smaller diameter than that ofcentral portion 176.Tape stock layer 211 is typically made of a thin layer of about 2 to 4 mils thickness of a plastic material like polypropylene or polyester or the like and is affixed to the top surface 110 with adhesive. - FIG. 8D illustrates another alternate embodiment of the
ID test rotor 16 of the present invention of FIG. 5 in which a thinflat recess 215, not shown to size, is formed in thetop surface 170 with dimensions to accepttape stock layer 211 withinrecess 215. Preferably,recess 215 has a depth of about 0.005 to 0.015 inches so that the top oftape stock layer 211 may be aligned below thetop surface 170 ofrotor 16. For purposes of clarity,tape stock layer 211 is not shown placed withinrecess 215. In such an embodiment, a number ofID rotors 16 may be stacked atop one another with thetop surface 170 of onerotor 16 in contact with thebottom surface 172 of anadjacent rotor 16. Recess 215 thereby prevents contact between thetape stock layer 211 and thebottom surface 172 of theadjacent rotor 16. In an exemplary embodiment, the features described in FIG. 8D are included in the rotor of FIG. 5. - FIG. 8E illustrates another alternate embodiment of the
ID test rotor 16 of the present invention in which theinclined annulus portion 188 further comprises aradial ridge 217 positioned proximate the first and second plurality ofmicrochannels annulus portion 188.Ridge 217 acts somewhat like a barrier in retaining a portion of sample fluids that are forced throughmicrochannels microwells microchannels - In a particularly useful embodiment,
rotor 16 comprises a body of polystyrene like Dow Chemical 666D or a similar moldable polymeric material and is about 0.015 inches thick and about 2 inches in diameter; microwells 178 and 182 are similar to one another in size and dimensions and have a diameter at the closed end in the range of about 0.090 to 0.094 inches; the walls of themicrowells microwells microchannels radial troughs surfaces flat bottoms 202 andtrough sidewalls 204 inclined at about 30-degrees thereto; theflat bottoms 202 are about 0.060 inches wide between the trough sidewalls 204 and the trough sidewalls 204 are about 0.060 inches high. - FIG. 10 is a perspective view of a closed elongate
ID rotor canister 32 having a generally rectangular cross-section formed by an IDcanister front wall 290, a five-section ID canister back wall 291 (FIG. 10B) and two IDcanister side walls 292, the IDcanister front wall 290, irregular ID canister backwall 291 and IDcanister side walls 292 are of dimensions so that a generally hexagonally shaped interior is formed to house a plurality ofID test rotors 16 stacked one atop another within therotor canister 32. Atop end portion 294 and abottom end portion 296 close the end portions ofrotor canister 32. A pair of bumpedsurface fingerpads 302 are formed inside walls 292 to facilitate handling by a operator. Key features of theID rotor canister 32 include an IDcanister mounting flange 300 shaped to seat into a mounting groove 301 (FIG. 1) within B/ID chamber 28 so that therotor canister 32 may be secured within mountinggroove 301 in a vertical position whereat two spring-loaded latching cams within B/ID chamber 28 engage a pair of rotor canister latch steps 304 formed as shown in a rotorcanister latching flange 306 extending slightly abovetop end portion 294. The portion of latchingflange 306 betweensteps 304 is confined between spring-loaded latching cams to provide proper vertical orientation. FIG. 10A is an enlarged view of the bottom endfront side portion 296 ofrotor canister 32 showing details of an ID rotor ejectport 308 formed in IDcanister front wall 290 proximate mountingflange 300 and sized to allow the lowermostID test rotor 16 within the plurality ofID test rotors 16 stacked one atop another to be pushed out ofrotor canister 32 by a plunger (not shown) and grasped byrobotic device 50. FIG. 10B is an enlarged view of the bottom end backside portion 296 ofrotor canister 32 showing a push-rod port 311 formed opposite ID rotor ejectport 308 so thatID rotors 16 may pushed out ofrotor canister 32 by a push-rod (not shown) and grasped byrobotic device 50. -
ID test rotors 16 may be grasped by a pair of clampingteeth 226 of ID robotic device 50 (FIG. 16) described later. ID rotor ejectport 308 has the shape of arectangular opening 312 formed between a pair ofrotor canister shoulders 310 projecting inwards fromwalls 292 and forming an opened rotor canister slit 313 at the top ofprotrusions 310. Anopen space 309 remains betweenshoulders 310. An upwardly projectingflexible tab 314 extends intorectangular opening 312 and serves to retainrotors 16 withincanister 32, preventing accidental dislodging of arotor 16 fromcanister 32 and also to preventrotors 16 from being improperly inserted back intocanister 32. Typically,canister 32 is formed as an indented sheet of plastic and is folded in half and sealed atflange 293 extending the full length ofrotor canister 32 between ID canisterfront wall 290 and five-section ID canister back wall (FIG. 10C). An opposed elongaterotor canister fold 295 is created in a sealing operation and also extends the full length ofrotor canister 32 between ID canisterfront wall 290 and five-section ID canister back wall. FIG. 10C is a sectional view ofrotor canister 24 and best illustrates theflange 293, fold 295, five-section ID canister backwall 291, two IDcanister side walls 292, and the IDcanister front wall 290. - FIGS.11A-11D and 12A-12B
show broth container 14 as adapted to be removed frombroth canisters 24 on the B/ID carousel 26 by brothcontainer handling apparatus 108, FIG. 21, and presented thereby to pipettingapparatus 46 within sample pipetting andtransport system 60. Thebroth container 14 has a generally octagonal body cross section (FIG. 11D) and is formed as a open container with features that provide for secure confinement withinbroth canisters 24 and for reliable handling by brothcontainer handling apparatus 108.Broth container 14 has a open top broth container surface 240 (FIGS. 11A and 12B) that is generally rectangular in shape except for four pairs ofears 239 created byindent notches 242 formed at opposing corners oftop surface 240.Ears 239 are sized and shaped so that a number ofbroth containers 14 may be confined inbroth canisters 24 in a common and stable orientation. The lower end ofinner sidewalls 243 ofbroth container 14 are seen in FIGS. 11A and 11B. - A key feature of
broth container 14, as best seen in FIGS. 11B, 11C, and 11D, is two pairs of opposing protrudingribs 248 formed on each of fourbroth sidewalls 250 and fully extending fromtop surface 240 to a outer bottombroth container surface 251 ofbroth container 14.Ribs 248 protrude about ⅛th inch outwards from broth container body sidewalls 250 and provide structural strength to eachbroth container 14 so that a number ofbroth containers 14 may be stacked atop one another inbroth canisters 24 without collapsing afoil membrane 29 that is adhered overtop surface 240 afterbroth containers 14 are filled with broth solutions. A sealingridge 241 is provided to aid in adheringfoil membrane 29 over thetop surface 240 ofbroth container 14. Becauseribs 248 fully extend fromtop surface 240 tobottom surface 251, whenbroth containers 14 are stacked atop one another withinbroth canisters 24 in the common and stable orientation assured byears 239, both pairs ofribs 248 of nextadjacent broth containers 14 are vertically aligned over another pair ofribs 248 and rest ontop surface 240 thereby providing structural protection to allbroth containers 14 confined withinbroth canisters 24. - Another key feature of
broth container 14, best seen in FIGS. 12A and 11D, is four Y-shapedclamping ridges 252 formed with theleg 252L of the Y-shapedclamping ridges 252 on four of broth container body sidewalls 253 belownotches 242 intop surface 240.Arms 252A of the Y-shapedclamping ridges 252 provide an important broth container clamping surface described hereinafter. Clampingridges 252 partially extend about 50% to 80% of the length ofsidewalls 253 towards thebottom surface 251 ofbroth container 14 and protrude about ⅛th inch outwards fromsidewalls 253. FIG. 11D shows two arm-portions 252A and leg-portion 252L ofbroth clamping ridges 252 so as to provide a vertically oriented recessed surface sized to mate withbroth clamping members 109 of brothcontainer handling apparatus 108. FIGS. 21, 21A and 21B illustrate how the clampingmembers 109 grip two clampingridges 252 in a pincher action. The two clampingmembers 109 are moveable relative to one another in a horizontal plane so that thelowermost broth container 14 inbroth canister 24 may be securely gripped by brothcontainer handling apparatus 108, removed from thebroth canister 24 and presented topipetting apparatus 46. - FIG. 13 shows another key feature of
broth container 14, or equivalentlysample tube 34, as being a freely disposed, ferromagnetic orsemi-ferromagnetic mixing member 254 that may be caused to revolve in a generally circular pattern within abroth container 14 or within asample tube 34 by avortex mixer 93 described in co-pending U.S. patent application Ser. No. 09/703,139. The mixingmember 254 may be caused to rapidly move by revolving an off-centermagnetic field source 258 having sufficient magnetic strength at high speed in a generally circular pattern in close proximity tobroth container 14 orsample tube 34. When themagnetic field source 258 is revolved as shown beneathbroth container 14, the mixingmember 254 is caused to move so as to minimize the distance separating the mixingmember 254 from themagnetic field source 258. Revolution of themagnetic field source 258 causes the mixingmember 254 to revolve within broth/sample solution 264 thereby generating a vortex-like mixing motion of broth/sample solution 264. In the embodiment described, adisk 266 encasesmagnetic field source 258 as shown. In the exemplary embodiment shown in FIG. 13, themagnetic field source 258 comprises a permanent orsemi-permanent magnet 258 andmagnetic mixing member 254 is caused to revolve by rotating the permanent orsemi-permanent magnet 258 at close proximity to thebroth container 14 using a mixingmotor 260 with a mixingmotor shaft 262 having thedisk 266 attached thereto. The term ferromagnetic is intended to mean a substance having a sufficiently high magnetic permeability to be positionally affected by an orbiting or rotating magnetic field. - FIG. 14 is a perspective view of a closed
elongate broth canister 24 having a generally rectangular cross-section (FIG. 14D) formed by a brothcanister front wall 320, ID canister backwall 321 and two IDcanister side walls 322, thefront wall 320,back wall 321 andside walls 322 of essentially similar dimensions so that a squarely shaped interior is formed to house a plurality ofbroth containers 14 stacked one atop another. Atop end portion 324 and abottom end portion 326 close the ends ofbroth canister 24. Typically,broth canister 24 is formed as an indented sheet of plastic and is folded in half creating aexternal rib 325 extending the full length ofbroth canister 24 between broth canister backwall 321 and a side wall 322 (FIG. 14B). An opposed elongate brothcanister seal flange 323 is created in a sealing operation and also extends the full length ofbroth canister 24 between broth canister backwall 321 and aside wall 322. A number of surface bumps 328 are formed in opposing pairs offinger pads 327 formed intop end portion 324 to facilitate handling of abroth canister 24 by an operator. FIG. 14B is a sectional view ofbroth canister 24 and best illustrates the brothcanister seal flange 323, broth canisterexternal rib 325 andinternal ribs 328. - Key features of the
broth canister 24 include a brothcanister mounting flange 324 shaped to seat into a mounting groove 331 (FIG. 1) within B/ID chamber 28 so that abroth canister 24 may be placed using a number offinger pads 327 in a vertical position whereat two spring-loaded latching cams within B/ID chamber 28 snap over latch steps 329 formed at opposing ends of a latching flange 330 extending upwardly abovetop end portion 324. The portion of latching flange 330 betweensteps 328 is confined between spring-loaded latching cams to provide proper vertical orientation. FIG. 14A is an enlarged view of thebottom end portion 326 ofbroth canister 24 showing details of abroth eject port 332 formed in brothcanister front wall 320 proximate mountingflange 324 and sized to allow thelowermost broth container 14 within the plurality ofbroth containers 14 stacked one atop another to be pulled out ofbroth canister 24.Broth containers 14 may be pulled out ofbroth canister 32 throughbroth eject port 332 bybroth clamping members 109 located at the end ofmoveable broth arms 238 of broth robotic device 108 (FIG. 21).Broth eject port 332 has the shape of a rectangular opening formed between a pair ofdepressions 334 having aflat portion 336 between thedepressions 334. Theflat portion 336 functions as a horizontal broth container sliding surface to supportbroth containers 14 as they are pulled out ofbroth canister 24 throughbroth eject port 332. A tongue flap projection 338 formed infront wall 320 extends downwardly and partially into theeject port 332 to preventbroth containers 14 from being dislodged accidentally fromcanister 24 and also to preventbroth containers 14 from being improperly inserted back intocanister 24. - FIGS.15A-15M illustrate the operation of sample pipetting and
transport system 60 of FIG. 3 in filling the AST test arrays of FIG. 5 in the previously mentionedAST carrier 74 “build and fill” process. FIGS. 15A-15L are simplified so as to clearly illustrate important improvements in high speed filling ofAST test arrays 12 andAST test microwells 124 with liquid sample aspirated fromsample tubes 34 by pipettingapparatus 46, and are an important advantage of the present invention, being derived from thesingle pipetting apparatus 46 being operational in two opposed directions along the single linear path defined by the loci L ofpositions 46 a-46 e as defined above such thatAST test arrays 12 may be filled with sample-inoculum at a plurality of positions along loci L. - Beginning with FIG. 15A, an
AST carrier 74 partially loaded withAST test arrays 12 and supported on ASTarray carrier bed 80B is seen positioned betweenAST carrier transporter 76 andAST array dispenser 84. In these FIGs., two identical AST array carrier beds are identified as 80A and 80B for purposes of discussion. ASTarray carrier bed 80A is seen as being empty in FIG. 15A. As discussed earlier,AST array dispenser 84 is adapted to removeAST test arrays 12 from anAST canister 18 in the form of a singulated stream and to successively place theAST arrays 12 within a number of emptyAST array slots 86 formed within anAST carrier 74 as theAST carrier 74 is advanced along a first direction on carried by ASTarray carrier bed 80B (arrow pointing “upwards” in FIG. 15A for purposes of illustration) as controlled byCPU 15. As indicated by the “upwards” direction of movement arrows, hereinafter called the “upwards direction”, the emptyAST carrier bed 80A is seen “ahead” ofAST carrier 74 on the AST array carrier bed BOB that is partially loaded withAST test arrays 12. The purpose of FIGS. 15A-15M is to describe how high speed filling ofAST test arrays 12 is accomplished as a result of thepipetting apparatus 46 operating in two opposed directions along the loci L defined bypositions 46 a-46 e taken withAST test arrays 12 being filled with sample-inoculum at a plurality of positions also along loci L. For purposes of clarity, ASTarray carrier transport 78 is shown only once in dashed lines in FIG. 15B and its two directions of travel are as indicated by a double-ended arrow even though the ASTarray carrier transport 78 is in each of FIGS. 15A-15M. - FIG. 15B illustrates a subsequent stage of
loading AST carrier 74 with ASTarrays 12, a stage in particular whereat afourth AST array 12 is being loaded ontoAST array carrier 74; pipettingapparatus 46, having aspirated an amount of inoculum-broth solution from abroth container 14, is atposition 46 d and deposits a known amount of inoculum-broth solution intoreservoir 134 of the firstAST test array 12 loaded ontoAST array carrier 74. As described before,pipetting apparatus 46 is controlled byCPU 15 between a third position, 46 c, for aspirating a known amount of inoculum-broth solution frombroth container 14 after the sample and broth are properly mixed together and a fourth position, 46 d, for depositing a known amount of sample and broth into anAST test array 12. As will be described in conjunction with these FIGS. 15A-15M,pipetting apparatus 46 “chases”AST array carrier 74 upwards or downwards as required so as to deposit inoculum-broth into allAST test arrays 12 carried byAST array carrier 74, eliminating the requirement thatAST arrays 12 be filled at a stationary position(s). Because pipettingapparatus 46 “chases”AST array carrier 74 to deposit inoculum-broth into theAST test arrays 12 carried thereby, an unnecessary need for extensive movement ofpipetting apparatus 46 is eliminated, thereby reducing the total time required forAST arrays 12 to be filled and increasing throughput ofanalyzer 10. It should be understood that pipettingapparatus 46 can begin to deposit inoculum-broth solution into thereservoir 134 of anAST test array 12 as soon as the firstAST test array 12 is loaded ontoAST array carrier 74. - This process continues until the requested number of
AST arrays 12 are loaded intoAST array slots 86 formed withinAST array carrier 74 at which stage the direction of motion of ASTarray carrier transport 78 reverses to a direction opposite the “upwards” direction, as indicated by the “downwards” direction of movement arrows, hereinafter called the “downwards direction”, in FIG. 15C. ASTarray carrier transport 78 continues in the downwards direction of movement until the empty ASTarray carrier bed 80A is aligned withAST carrier transporter 76 at which stage, FIG. 15D, ASTarray carrier transport 78 is stopped and anempty AST carrier 74 is moved byAST carrier transporter 76 onto ASTarray carrier bed 80A. At this stage, the direction of motion of ASTarray carrier transport 78 reverses once again to the “upwards direction” (FIG. 15E). The emptyAST array carrier 74 is obtained by 30AST carrier transporter 76 from within a number of similar anempty AST carriers 74 made available within AST incubation andanalysis chamber 70. During this time,pipetting apparatus 46 continues to “chase”AST array carrier 74 and deposit at the “moving”position 46 d a known amount of inoculum-broth into theAST test arrays 12 on theAST array carrier 74 until allAST arrays 12 are filled. - This movement in the “upwards direction” continues until the
AST array carrier 74 having all filledAST arrays 12 is in alignment withAST carrier transporter 76 at which stage, FIG. 15F, ASTarray carrier transport 78 is stopped andAST carrier transporter 76 removes anAST array carrier 74 from ASTarray carrier bed 80B and lowers theAST array carrier 74 throughAST transport opening 81 in operatingplate 11 to a lowermost position whereat theAST carrier transporter 76 deposits theAST array carrier 74 into the ASTvacuum filling station 82 positioned on thelower base plate 13. After depositingAST array carrier 74 in the ASTvacuum filling station 82,AST carrier transporter 76 moves vertically alongAST transport rod 83 to anAST incubation rack 72 and removes an unloadedAST carrier 76 from AST incubation andanalysis chamber 70 through openedside portion 73 formed in the exterior wall of theAST incubation chamber 60. WhenAST carrier transporter 76 removes ASTarray carrier 74 from ASTarray carrier bed 80B, the direction of motion of ASTarray carrier transport 78 reverses once again to the “downwards direction” (FIG. 15G) so that the previously unloadedAST array carrier 74 may be loaded withAST arrays 12 byAST array dispenser 84 as shown. As before, as soon as a singleAST test array 12 has been loaded ontoAST array carrier 74,pipetting apparatus 46 “chases”AST array carrier 74 to deposit inoculum-broth into theAST test arrays 12 carried thereby. This process continues until the stage depicted in FIG. 15H is reached, when allAST array slots 86 within ASTarray carrier 74 are filled at which stage the direction of motion ofAST array carrier 74 reverses to the “upwards direction”. - Filling of
AST arrays 12 on ASTarray carrier 74 by pipettingapparatus 46 continues until the empty ASTarray carrier bed 80B is in alignment withAST carrier transporter 76 at which stage, FIG. 15J, ASTarray carrier transport 78 is stopped and an unloadedAST array carrier 74 is placed on empty ASTarray carrier bed 80B byAST carrier transporter 76, and the direction of motion of ASTarray carrier transport 78 reverses once again to the “downwards direction” (FIG. 15K). During this stage, as soon as a singleAST test array 12 has been loaded ontoAST array carrier 74,pipetting apparatus 46 “chases”AST array carrier 74 to deposit inoculum-broth into theAST test arrays 12 carried thereby. FIG. 15K illustrates an important portion of the movements during whichpipetting apparatus 46 is at fixedposition 46 c to aspirate inoculum-broth solution frombroth container 14 as it also “chases”AST array carrier 74. - Movement in the “downwards direction” continues (FIG. 15K) until the
AST array carrier 74 having all filledAST arrays 12 is in alignment withAST carrier transporter 76 at which stage, FIG. 15L, ASTarray carrier transport 78 is stopped, theAST array carrier 74 is removed byAST carrier transporter 76; the direction of motion of ASTarray carrier transport 78 reverses once again to the “upwards direction” so that the unloadedAST array carrier 74 on 80B may next be loaded withAST arrays 12 byAST array dispenser 84. - As before the
AST array carrier 74 loading process begins and as soon as anunfilled AST array 12 is positioned uponAST array carrier 74,pipetting apparatus 46 begins depositing a known amount of inoculum-broth into anAST test array 12. This situation exactly replicated the AST array loading and filling stage of FIG. 15A enabling the AST array filling process to continue without stopping by automatically proceeding to theAST array 12 filling stages depicted by FIGS. 15A-M. - It should be understood that the feature of
analyzer 10 in which asingle pipetting apparatus 46 operational in two opposed directions along a single linear path defined by the loci ofpositions 46 a-46 d as defined above provides a degree of compactness in layout in addition to minimizing the amount of time required in the AST array filling process. - FIG. 19 illustrates
AST array dispenser 84 adapted to remove or ejectAST test arrays 12 from anAST canister 18 in the form of a singulated stream ofAST test arrays 12 and to successively place each of theAST arrays 12 within an emptyAST array slot 86 formed within anAST array carrier 74.AST array dispenser 84 comprises apushrod 368 controlled byCPU 15 to displace anAST array 12 from anAST canister 18 and into contact with anarray alignment wall 360 and between thealignment wall 360 and anarray guide 362 to precisely position the lowermostAST test array 12 within an emptyparallel slot 86 in anAST array carrier 74.Array guide 362 is biased towardsarray alignment wall 360 byarray guide spring 364 to maintain alignment of anAST array 12 being moved from anAST canister 18 into an emptyAST array slot 86 during the process ofloading AST arrays 12 onto aAST array carrier 74. AnAST array lifter 369 is also located below and between thealignment wall 360 and thearray guide 362 to lift anAST array 12 above thebase 75 of carrier 74 (FIG. 17) as theAST array 12 is placed within an emptyAST array slot 86 in order to protect the layer of adhesive film along thebottom surface 120 ofAST array 12 previously mentioned. - FIG. 20 illustrates one of several alternate embodiments of a
AST carrier transport 78 adapted to transport an emptyAST carrier bed 80 or anAST carrier bed 80 having anAST array carrier 74 totally filled withAST arrays 12 or partially loaded withAST arrays 12 during the loading process of FIG. 15. In one embodiment,AST carrier transport 78 comprises at least one AST carrier transport take uproller 380 which drives abelt 382 in two directions along a linear path overupper operating plate 11 as illustrated in FIG. 15. BothAST carrier beds 80 are fastened to the ASTcarrier transport belt 382 usingpins 386. ASTcarrier transport belt 382 is moved along a linear path beneath sample pipetting anddelivery system 60 during whichmovement AST carriers 74 may be loaded withAST arrays 12, andAST arrays 12 may be filled with a known amount of inoculum-broth by pipettingapparatus 46 atposition 46 d. Alternate embodiments ofAST carrier transport 78 include use of a lead screw-driven follower to supportAST carrier beds 80. - The ID robotic device50 (FIG. 16) typically comprises a computer controlled motor-driven apparatus adapted for movement in x-y-z, and radial directions so as to move
ID rotors 16 withinanalyzer 10 as previously described.Device 50 may take on many alternate designs but typically includes rack and pinion gears 222 and/or arotating gear mechanism 56 to control the clamping of and movement ofID rotors 16. An important feature ofdevice 50 is at least one pair of clampingteeth 226 located at the end ofmoveable arms 58 and maintained by atension spring 57 to provide a spring-activated normally-closed incisor force. Clampingteeth 226 are sized to fit intotroughs secure ID rotor 16 for movement as required withinanalyzer 10. In the event of a power failure, anyID rotor 16 held within clampingteeth 226 is retained securely because of normally-closed, spring-activation clamping action ofdevice 50. Flexible and secure transportation of anID rotor 16 between the automated stations ofanalyzer 10 is made possible by the presence oftroughs ID rotor 16 may be thereby constrained by any number of differently designedrobotic devices 50. - ID
robotic device 50 is further adapted to removeID test rotors 16 from the filling and centrifuging apparatus 52 (when centrifugingapparatus 52 is positioned within the ID incubation chamber 48) to either arotor holding frame 228 or to ID rotoroptical analyzer 230 both of which are located within the ID incubation and analysis chamber 48 (FIG. 1). IDrobotic device 50 is additionally adapted to moveID test rotors 16 from arotor holding frame 228 to arotor disposal station 49 within theID incubation chamber 48. In an exemplary embodiment, as many as fourrotor holding frames 228 may be attached to the interior walls of theID incubation chamber 48 and as many as twentyID test rotors 16 may be mounted within eachrotor holding frame 228. Typically,rotor holding frames 228 are horizontally oriented C-clamp shaped pieces of spring metal in which the ears of the holding frames 228 are adjusted to provide an interference fit between the holdingframes 228 and anID rotor 16. - The broth container handling apparatus108 (FIG. 21) typically comprises a computer controlled rack and
gear system 234 to control the clamping of and movement ofbroth containers 14. An important feature of brothcontainer handling apparatus 108 is at least one pair of clampingteeth 109 located at the end ofmoveable arms 238 and maintained by atension spring 236 to provide a spring-activated normally-closed incisor force. Clampingteeth 109 are sized to fit over thearm portion 252A of the Y-shapedclamping ridges 252 as seen in FIG. 21B and therebysecure broth containers 14 for movement as required withinanalyzer 10. FIG. 21A shows the automatic opening action ofteeth 109 asarms 238 are advanced towards abroth container 14 and moved outwards as theteeth 109 ride over thearm portion 252A of the Y-shapedclamping ridges 252. In the event of a power failure, anybroth container 14 held within clampingteeth 109 is retained securely because of normally-closed clamping action ofdevice 108. A pair oftapered cams 370 are shown onarms 238 so that when an usedbroth container 14 is to be disposed in a trashing chute (not shown),arms 238 may be spread by a pair of mating rollers (not shown) andbroth container 14 released into the chute. A slottedkeeper 111 is seen as retaining aprotruding rib 248 onbroth sidewalls 250 so that abroth container 14 is held betweenarms 238 during the disposal process and not allowed to cling to either of theteeth 109. Flexible and secure transportation of abroth containers 14 between the automated stations ofanalyzer 10 is made possible by the presence of the Y-shapedclamping ridges 252 in conjunction withteeth 109 as thebroth containers 14 may be transported by any number of differently designedrobotic devices 108. - The ID rotor
optical analyzer 230 may have several embodiments but typically comprises a fluorometric reader similar to that used in the MicroScan “WalkAway® microbiology analyzer sold by Dade Behring Inc., Deerfield, Ill. U.S. Pat. Nos. 4,676,951, 4,643,879, 4,681,741 and 5,645,800 describe certain features of the WalkAway® analyzer. The ID rotoroptical analyzer 230 typically includes a pair of stationary reading heads that reside above the two annular arrays of test microwells 178 and 182 inID rotor 16 whenrotor 16 is placed within ID rotoroptical analyzer 230. Each reading head encloses a fluorometer having a source that directs interrogating radiation to an excitation filter through a light path. A pair of lenses or dichromatic beam splitters direct the outcoming radiation onto sample contained either inmicrowells ID rotor 16. The microwell is preloaded with a material that, in the presence of a target microorganism within sample fluids displaced into the microwells as described hereinafter, reacts to the light energy by fluorescing. The resulting fluorescence is directed by lenses or mirrors to an emission filter for the expected wavelength. Solid state detectors capture the fluoresced light signal from each ofwells board CPU computer 15 so that the pattern of signals emanating from themicrowells - ID rotor filling and centrifuging apparatus52 (FIG. 22) comprises a
moveable arm 206 mounted to arotatable support 208 rotated by aCPU 15 computer-controlledmotor 210 so thatarm 206 may be rotated in a plane between ID incubation andtesting chamber 48 and rotor filling and centrifugingposition 46 e located along loci L serviced by sample pipetting andtransport system 60. An important feature of the filling and centrifugingapparatus 52 is acentrifuging module 212 adapted to both provide rotational motion to anID rotor 16 mounted within a IDrotor clamping mechanism 214 and to present anID rotor 16 to pipettingapparatus 46 at the fifth position, previously identified as 46 e, in order that a known amount of sample may be deposited into anID test rotor 16.Centrifuging module 212 typically comprises a centrifugingmotor 216 capable of rotatingID rotor 16 via a centrifugingbelt drive 218 at an initial relatively low speed in the range of about 200 to 400 RPM and also at a relatively high speed in the range of about 3,500 to 4,500 RPM. IDrotor clamping mechanism 214 is adapted to graspID rotor 16 at its periphery when theID rotor 16 is pushed horizontally onto centrifugingmodule 212 or to secureID rotor 16 with latches if therotor 16 is moved vertically into centrifugingmodule 212. As described later, liquid sample is initially loaded intorotor 16 in a low RPM operation and then moved to microwells 178 and 182 in a higher RPM operation.Centrifuging module 212 is also operable so that after anID rotor 16 is loaded with sample,arm 206 may be rotated from rotor filling and centrifugingposition 46 e back into ID rotoroptical analyzer 230 within ID incubation andtesting chamber 48 and rotated slowly during the optical analysis process.Motor 216 that enables the rotational functions of centrifugingmodule 212 are known in the art as variable speed motors and are commercially available from a number of sources. - During operation of
analyzer 10, patient samples to be tested have bar-coded identifying indicia from which the ID and AST tests that are desired to be accomplished may be identified.Analyzer 10 is programmed using well-known computer-based programming tools to automatically perform the appropriate sample and reagent handling protocols.Computer CPU 15 is programmed to automatically determine aparticular ID canister 32 having the appropriateID test rotors 16 required to complete the requested ID protocol(s), to rotate B/ID carousel 26 to present theappropriate ID canister 32 to therobotic device 50.Robotic device 50 removes anID test rotor 16 from the selectedID canister 32 by gripping thetroughs teeth 226, moves the selectedID test rotor 16 intoID incubation chamber 48 and then loads therotor 16 onto the filling and centrifugingapparatus 52. At the same time, sample pipetting anddelivery system 60 is controlled byCPU 15 to make available atposition 46 e the required amount of sample for the ID protocol to be performed. Filling and centrifugingapparatus 52 next movesID test rotor 16 intoposition 46 e where sample for the ID protocol is deposited intorotor 16 throughopening 213 intape 211. - While the
rotor 16 is loaded with sample, centrifugingmodule 212 portion of filling and centrifugingapparatus 52 is activated to rotateID rotor 16 at an initial relatively low speed in the range of about 200 to 400 RPM for a period of time in the range 1-3 seconds during which sample is moved away from the centermost portion ofsurface 176 and upwards alongsurface 188. Thecentrifuging module 212 is next activated to rotateID rotor 16 for a period of time in the range 5-15 seconds at a speed in the range of about 3,500 to 4,500 RPM during which sample is moved throughmicrochannels microwells ID rotor 16 is stopped,ridge 217 acts as a barrier to retain excess sample portion which is sacrificially evaporated over time thereby eliminating evaporation of sample withinmicrochannels - Filled
IR rotors 16 are next moved back into ID incubation andtest chamber 48 by filling and centrifugingapparatus 52 whererotors 16 may be initially read by ID rotoroptical analyzer 230.Robotic device 50 then placesIR rotors 16 into incubation frames 228 for various periods of time, depending on the particular ID test protocol being performed byanalyzer 10 under control ofCPU 15. As is known, during incubation, fluorescence signals emanating from loadedmicrowells robotic device 50 to moveID rotors 16 to and fromracks 228 as required and to and from ID rotoroptical analyzer 230. After the completion of an ID test protocol,ID rotors 16 are deposited intrash receptacle 49. - In a similar manner, the analyzer is also programmed to automatically select the numbers of different
AST test arrays 12 andbroth containers 14 required to complete the requested AST tests.AST canister post 20 is automatically rotated to present theAST canisters 18 containing the requiredAST test arrays 12 to ASTarray dispenser 84 and to load theAST test arrays 12 onto ASTcarriers 74 for transportation to various filling, incubation and testing stations. - Filled
AST arrays 12, using the process described in FIGS. 15A-M, are transported byAST carrier transporter 76 to thearray filling station 82 where inoculum-broth solution is dispersed to alltest microwells 124 in theindividual arrays 12 using vacuum-filling means. To fill themicrowells 124 with an inoculum-broth solution to be tested,pipetting system 46 dispenses a predetermined quantity of inoculum-broth solution intoreservoir 134 within eachAST test array 12 carried onAST carriers 74 as described in conjunction with FIG. 15. When all of thereservoirs 134 have been loaded with inoculum-broth solution,AST carrier transporter 76 moves theAST array carrier 74 to AST arrayvacuum filling station 82 where a clam-shell like vacuum chamber is lowered over theAST array carrier 74 and a vacuum is applied to allAST test arrays 12 carried thereon.Vacuum filling station 82 used to fill test wells inAST test arrays 12 employs techniques that are generally known in the art and typically includes means to generate and release a vacuum within anAST test array 12 and consists generally of a vacuum pump, appropriate vacuum control valves, air filters and pressure transducers that are controlled byCPU 15 to apply and release vacuum in a manner to not cause an excessive amount of bubble formation when thesealable air port 138 is sealed and theAST test array 12 released to atmospheric pressure. When vacuum is applied around thetest arrays 12, air is removed from all AST microwells 124 through thesealable vacuum port 138 which is in fluid communication with individual AST microwells 124 by means ofmicrochannels vacuum port 138 and heated by electrical current for a predetermined time to seal orclose port 138 against air flow when vacuum is released; onceport 138 is sealed, the vacuum is released within vacuum chamber. Alternately, a resilient stopper may be pressed against an air port separate from the evaporation well as previously described. Atmospheric pressure over the inoculum-broth solution inreservoir 134 causes inoculum-broth solution to flow throughopening 140 intomicrochannels microwells 124 in each of theAST test arrays 12 carried byAST array carrier 74. As themicrowells 124 are filled with inoculum-broth solution, all remaining air trapped within thechamber 158 will flow into the small recessedtop edge portion 160 which acts as a bubble trap withinmicrowell 124. - The
AST test arrays 12 are removed fromvacuum filling station 82 and transported to the analysis andincubation chamber 70 byAST carrier transporter 76. AST testing may be accomplished within analysis andincubation chamber 70 byAST array reader 90 using a beam of interrogating radiation from above or below eachAST array 12 through the polishedcentral arc portion 157 of thetop surface 150 of eachmicrowell 124 and measuring the degree of absorption or change in color or generation of a fluorescent signal using a calorimetric or fluorometric photodetector located below or above eachmicrowell 124. - Broth is supplied to the
analyzer 10 inprefilled broth containers 16 typically containing four different types of broth.CPU 15 is programmed to automatically identify the type ofbroth container 16 needed to perform the requested AST tests and to rotate B/ID carousel 26 to present therequisite broth container 14 to the brothcontainer handling apparatus 108 and thereby to pipettingapparatus 46. As described previously,pipetting apparatus 46 is adapted to remove a known amount of inoculum from asample tube 34 and deposit inoculum intobroth container 14 atposition 46 c where inoculum and broth are mixed usingvortex mixer 93, and then aspirated from thebroth container 14 as an inoculum-broth solution and deposited into the aforementioned inoculum-broth reservoir 134 ofindividual test arrays 12. - It is to be understood that the embodiments of the invention disclosed herein are illustrative of the principles of the invention and that other modifications may be employed which are still within the scope of the invention. Accordingly, the present invention is not limited to those embodiments precisely shown and described in the specification but only by the following claims.
Claims (21)
Priority Applications (4)
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EP02756966A EP1335971A4 (en) | 2001-08-08 | 2002-07-30 | Automated random access microbiological analyzer |
JP2003519222A JP2004537319A (en) | 2001-08-08 | 2002-07-30 | Automatic random access microbial analyzer |
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US6573088B2 (en) | 2003-06-03 |
EP1335971A4 (en) | 2005-09-14 |
WO2003014290A1 (en) | 2003-02-20 |
EP1335971A1 (en) | 2003-08-20 |
JP2004537319A (en) | 2004-12-16 |
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